Journal
NEOPLASIA
Volume 9, Issue 8, Pages 662-670Publisher
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.07433
Keywords
angiosarcoma; galectin-3; chemotherapy; doxorubicin; apoptosis
Categories
Funding
- NCI NIH HHS [R37 CA046120, 5R01 CA89827, R37 CA046120-19, P01 CA093900, P50 CA069568, R01 CA089827, P50 CA69568, P01 CA093900-01A2] Funding Source: Medline
- NHLBI NIH HHS [R01 HL078816] Funding Source: Medline
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Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a beta-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA and canine HSA and could play an important role in malignant endothelial cell biology. Immunohistochemical analysis demonstrated that 100% of the human ASA ( 10 of 10) and canine HSA ( 17 of 17) samples analyzed expressed Gal-3. Two carbohydrate-based Gal-3 inhibitors, modified citrus pectin (MCP) and lactulosyl-L-leucine (LL), caused a dose-dependent reduction of SVR murine ASA cell clonogenic survival through the inhibition of Gal-3 antiapoptotic function. Furthermore, both MCP and LL sensitized SVR cells to the cytotoxic drug doxorubicin to a degree sufficient to reduce the in vitro IC50 of doxorubicin by 10.7-fold and 3.6-fold, respectively. These results highlight the important role of Gal-3 in the biology of ASA and identify Gal-3 as a potential therapeutic target in tumors arising from malignant endothelial cells.
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